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- W2400142783 abstract "Background Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40–50%) and liver tests abnormalities (40–70%). In HNF1B patients who reach end-stage renal disease, single kidney (SKT) or combined kidney-pancreas transplantation (KPT) can be considered. Methods A retrospective multicenter study including 18 HNF1B patients receiving SKT or KPT, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure. Results Following SKT, 50% of the HNF1B patients develop early post-transplantation diabetes mellitus (PTDM), while 40% experience new-onset or severe worsening of pre-existing abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independently of NFATc. Conclusions Because HNF1B -related disease is a heterozygous condition, calcineurin inhibitors used to prevent rejection may induce reduced expression of the non-mutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of PTDM and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B , and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach." @default.
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- W2400142783 date "2016-06-01" @default.
- W2400142783 modified "2023-10-17" @default.
- W2400142783 title "Calcineurin inhibitors down-regulate HNF-1β and may affect the outcome of HNF1B patients after renal transplantation" @default.
- W2400142783 doi "https://doi.org/10.1016/j.arcped.2016.03.022" @default.
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